Many drugs are administered in racemic form and others undergo metabolism to form chiral metabolites. The chiral nature of most biologically important molecules inevitably results in differences between drug enantiomers in transport, binding and metabolism, hence differences in biological acitivity. Establishing a relationship between pharmacol gical activity, toxicology and stereoselectivity of metabolic processes may lead to the production of new and better drugs and to better use of present drugs. Quantitation of the individual enantiomers in biological systems is of importance in studying the stereochemical differences but is extremely difficult due to the inherent similarity of enantiomers. We have shown that stereoselective antibodies for warfarin, pentobarbital, secobarbital, thiopental and thiamylal can be obtained and utilized in radioimmunoassay (RIA) procedures for the determination of one enantiomer in the presence of the other. We propose to extend this work to cover other members of the class of coumarin anticoagulants and optically active barbiturates. We propose to synthesize optically pure haptens based on drug molecules, conjugate them to protein and use the conjugates to induce antibody formation in animals. Optically pure drug enantiomers will be radiolabeled and used in conjunction with the antibodies to develop stereoselective RIA's. The developed assays will be used to study species differences in enantiomer disposition, as well as the effects of stimulants and depressants of the hepatic microsomal enzyme system and the effects of age. Drug interaction effects, as well as effects of age, sex and disease, on enantiomer metabolism may be of clinical significance. In addition, studies of enantioselective metabolism offer a sensitive tool for probing the basic nature of the drug metabolizing enzymes.